Amoxicillin Less Effective than Ampicillin against Shigella in Vitro and in Vivo: Relationship of Efficacy to Activity in Serum

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Abstract
Minimal inhibitory concentrations of amoxicillin and ampicillin against Shigella are similar. Infants and children hospitalized for shigellosis were treated with amoxicillin (25 or 50 mg/kg per day) or ampicillin (50 mg/kg per day) given orally. Dose-response curves demonstrated that, with equivalent dosage, mean peak levels in serum were three times as high after amoxicillin as after ampicillin (8.7 µg/ml vs, 3.0 µg/ml), and one-half the dose of amoxicillin gave a mean peak level in serum of 5.3 µg/ml. However, amoxicillin failed to effect a bacteriologic or clinical cure. of shigellosis. The apparent paradox of pharmacologic superiority but clinical inferiority of amoxicillin to ampicillin correlated with the lesser inhibitory power of amoxicillin in serum. Approximately twice the amount of amoxicillin in serum was required for comparable inhibition of the infecting strain of Shigella as determined from studies of specimens of patients' sera and from in vitro experiments with known amounts of the two drugs added to pooled normal human serum.

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